Validation and Cryopreservation of Ligament Engineered from Human Bone Marrow

DESCRIPTION provided by applicant The founders of Skeletal Tissue Engineering Laboratory Technologies LLC STEL are researchers at the University of Michigan Our research team has developed an innovative and paradigm shifting approach to ligament tissue engineering and a unique methodology for ACL replacement This tissue engineered ligament technology offers the possibility of radical improvements in outcomes for patients who suffer acute knee injury This strategy avoids the poor biomechanical limitations of current ACL replacement strategies with patellar or hamstrings tendons or cadaver tissues The advantage of our method over other synthetic and native scaffold based technologies including those coated with growth factors is that our bone marrow stromal cell BMSC derived bone ligament bone BLB graft is a biological solution that has the developmental regenerative potential to induce cellular migration differentiation and tissue remodeling and tissue regeneration into a mature ligament To date the efficacy of these constructs for ACL repair has been tested in four long term mo mo and mo studies in a large animal model the sheep To develop a product with clinical applications two pressing issues must be resolved First we must confirm that the BLB can be fabricated from human BMSCs without toxins or bio incompatible agents and resolve the safety concerns associated with the use of a progenitor cell population in repair processes as our first aim One of the unique qualities of our engineered graft is that it is a livng tissue with unique biomechanical properties However bringing live tissue to a human patient population is a logistical challenge Thus the second issue is packaging shipping and storage of the living tissue before surgical implantation Therefore the second aim will investigate several commercially available cryopreservation solutions to optimize the process of freezing and reconstituting BLB grafts while maintaining cell viability and biomechanics of the engineered ligament The ability to utilize commercially available cryopreservation solutions in order to maintain the cell viability and biomechanics of the engineered ligament would enhance the translational capabilities of this technology The success of this STTR will result in the development of an andquot off the shelfandquot human ligament graft ready for use in ACL repairs PUBLIC HEALTH RELEVANCE Approximately anterior cruciate ligament ACL reconstruction surgeries are performed in the US each year and billions of dollars are spent on the acute care costs involved in these procedures The most common ACL replacement strategies involve autogenic or allogenic tendon grafts that never fully integrate with the bone tunnel created during surgery and knee joints that do not recover pre injury level biomechanics Our innovative and paradigm shifting approach to ligament replacement offers the possibility of a radical improvement in outcomes for patients who suffer acute knee injury including the complete restoration of native knee biomechanics and potential reductions in associated early onset of osteoarthritis